(1) Field of Invention
The present invention relates to an improved process for preparing fluoroaromatics or fluoropyridines by diazotization-fluorination of corresponding aromatic or heterocyclic amines in hydrogen fluoride. More particularly, the invention relates to processes in which a suitable amine substrate is diazotized with a diazotization reagent in hydrogen fluoride to form a corresponding diazonium fluoride and the diazonium fluoride is decomposed to form a corresponding aromatic or aromatic or heterocyclic fluoride. Specifically, the invention relates to an improved process in which the diazotization-fluorination is conducted in a solution of hydrogen fluoride containing selected tertiary amine compounds.
(2) Prior Art
Osswald et al, German Pat. No. 600,706 disclosed the conventional two-step process for diazotization-fluorination of primary aromatic amines utilizing sodium nitrate and anhydrous hydrogen fluoride. A solution was made of the amine in hydrogen fluoride and sodium nitrite was added, the temperature during addition being held below about 10.degree. C until diazotization is complete. After completion of diazotization, the reaction mixture is refluxed (temperature 30.degree. C-40.degree. C) to decompose the diazonium fluoride, yielding nitrogen and the corresponding aromatic fluoride. Ferm and Vander Werf, J. Am. Chem. Soc., 72, 4809 (1950) expanded this technology to include other substrates. Shenk et al, U.S. Pat. No. 2,563,796 modified the process by utilizing gaseous nitrosyl chloride rather than sodium nitrite in order to obtain higher decomposition temperatures.
The Osswald et al and Ferm and Vander Werf teachings have been applied to numerous aromatic and heterocyclic amine substrates and their work-up procedures have been modified over the years to improve yields and facilitate product recovery.
Nevertheless, there is still a need for further improvement and efforts have been made to modify reaction conditions to obtain increased yields and/or further simplify the overall process. One such example is found in Misaki et al, Japanese Patent Publication 81330/74, published Aug. 6, 1974 pursuant to Japanese Application 126570/72, filed Dec. 15, 1972. In accordance with this teaching, improved yields were reportedly attained in a single step diazotization-decomposition by dissolving a diazotization agent, such as sodium nitrite, in excess anhydrous hydrogen fluoride (generating nitrous acid in HF), separately dissolving the diazotizable amine in hydrogen fluoride, then adding the diazotization compound in HF to the amine in HF at temperatures in the range of 30.degree. C-50.degree. C to simultaneously form and decompose the diazonium fluoride to the aromatic fluoride.
De Milt et al, J. Am. Chem. Soc. 58, 2044 (1936) disclosed that pyridine and certain other tertiary amines combined with an excess of strong mineral acid such as H.sub.2 SO.sub.4 were good solvents for the diazotization of weakly basic and insoluble anilines. And, Spietschka, U.S. Pat. No. 3,888,841 disclosed this was also true in an alkaline environment in the presence of nitrosylsulfuric acid or nitrosyl chloride. Neither reference, however, teaches or suggests the use of tertiary amine compounds as described herein or the fluorination of amines utilizing hydrogen fluoride.
Boudakian et al, U.S. Pat. No. 3,798,228 discloses the preparation of difluoropyridine by tetrazotization-fluorination of suitable diaminopyridines with a diazotization reagent and hydrogen fluoride. Boudakian, U.S. Pat. No. 3,703,521 discloses the preparation of 4-fluoropyridine and its salts by this route utilizng a modified work-up procedure to stabilize the end product. Boudakian, German Offenlegungsschrift 2,113,253, discloses an integrated route to m-fluoroaniline by diazotization-fluorination of m-aminoacetanilides with sodium nitrite and hydrogen fluoride.
Kollonitsch, U.S. Pat. Nos. 3,471,511 and 3,573,214 and Kollonitsch et al., 3,471,512 discloses a process in which the diazotization-fluorination of aromatic amines is conducted in the absence of dimethylsulfoxide (DMSO) in HF. While the use of this mixture appears to have a beneficial effect on yields in many instances, this improvement is offset by high DMSO requirements and by severe corrosion which occurs in this media, making it commercially unattractive.
Research has also been carried out in the area of halogen exchange on aromatic or heterocyclic substrates. See Abramovitch, Pyridine and Its Derivatives, Supplement, Part Two, Vol. 14, pages 421-23 (1974) and Raphael et al, Advances in Organic Chemistry, Methods and Results, Vol. 5, pages 30 and 31, (1965). Here the halo groups on aromatic or heterocyclic substrates are exchanged for fluoro groups by the reaction with potassium fluoride. The chemistry is different than the present invention wherein both diazotization and fluorination is carried out in one medium of hydrogen fluoride containing selected tertiary amine compounds.
It has now been found that whether one employs the conventional two-step process or its modification or the one-step process, the presence of selected tertiary amine compounds in the hydrogen fluoride solution or medium, surprisingly and unexpectedly, enhances yields beyond those obtainable when diazotization is conducted in HF alone. It has also been found that the presence of tertiary amine compounds in HF will not result in equipment corrosion as has been found with DMSO. Further, it has been discovered that these compounds need only be used in low concentrations and that their presence simplifies product recovery by improving phasing of organic and inorganic layers. Moreover, the use of these compounds permits diazotization-fluorination in HF of substrates which previously with HF alone gave principally tars.